Glucocorticoids are effective therapy for leukemia and lymphoma (ML), yet response is highly variable and toxicity common. To identify patients likely to respond, we have developed and applied several in vitro assays to patients' tumor cells and correlated these with response to single-agent glucocorticoid therapy. Our data suggest that tumor glucocorticoid receptor (GR) levels predict response in some disease types. The primary objective of this renewal is to continue to define those in vitro characteristics that will allow selective use of steroids in treating leukemia and ML. We will do this by extending our ongoing study of ML and ALL (relatively glucocorticoid sensitive diseases) to CLL and ANLL (relatively glucocorticoid resistant diseases). In vivo response to glucocorticoids in each disease category and subcategory will be correlated with tumor GR levels and in vitro glucocorticoid sensitivity. In addition, we will expand our studies, using new techniques from our laboratories, to include evaluation of the functional and molecular properties of the receptors. Specifically, we will study various forms of cytoplasmic glucocorticoid-receptor complexes (activated, nonactivated, biologically inactive) and the size (molecular weight) and charge of the receptor protein(s). In T-cell tumors, where we find poor correlation between GR levels and in vivo response we will study the interaction of T-cell growth factor and glucocorticoids, since new data suggest that they have opposing effects on growth of neoplastic T-cells. This research continues a unique collaboration among investigators at the University of Minnesota (experts in clinico-pathologic studies in leukemia and ML) and Dartmouth and the NIH (experts in in vitro glucocorticoid studies). Patients are diagnosed and treated at Minnesota; in vitro studies of their malignant cells are done at Dartmouth and the NIH. Results of in vitro glucocorticoid analyses are correlated with each other, morphology, surface markers, treatment status and in vivo antitumor response to single-agent glucocorticoid therapy. This research should enable us to individualize glucocorticoid therapy in leukemia and ML so that patients likely to benefit can receive them and those unlikely to respond can be spared significant toxicity. On a more basic level, we should increase our understanding of the mechanisms of glucocorticoid sensitivity and resistance.